Theoretical investigation of protein search for targets on DNA

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dc.contributor.advisorKolomeisky, Anatoly Ben_US
dc.creatorKochugaeva, Mariaen_US
dc.date.accessioned2019-05-16T20:38:03Zen_US
dc.date.available2019-05-16T20:38:03Zen_US
dc.date.created2017-08en_US
dc.date.issued2017-08-11en_US
dc.date.submittedAugust 2017en_US
dc.date.updated2019-05-16T20:38:03Zen_US
dc.description.abstractProtein-DNA interactions activate many biochemical transitions used by living systems for successful functioning. The starting point in this process is a protein search and recognition of specific target sequences on DNA among millions of non-specific sites. One of the most striking observations is the fact that some proteins can find their targets on DNA much faster than expected from 3D bulk diffusional estimates which follow from the famous theory developed by M.Smoluchovski. This phenomenon is known as facilitated diffusion. After extensive investigation via theoretical and experimental methods, it has been argued that the facilitated diffusion of proteins (also known as accelerated search) is possible due to combining 3D bulk motion with 1D sliding of non-specifically bound protein molecules along the DNA chain. The recent development of single-molecule techniques has allowed for direct visualization of protein sliding during its binding site search. Thus, although we now have a better understanding of protein search on DNA, there are still many unanswered questions and many features related to this complex biological phenomenon that are still not resolved at the molecular level. In this work we develop a theoretical method to explain the molecular picture behind these complex processes. Our approach is based on a discrete-state stochastic framework and utilizes a first-passage probability method that takes into account the most relevant physical-chemical processes. This allows us to explicitly evaluate the protein search for the targets on DNA for different conditions. Theoretical predictions are supported by Monte Carlo computer simulations, and obtained results are utilized for analysis of available experimental data.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationKochugaeva, Maria. "Theoretical investigation of protein search for targets on DNA." (2017) Diss., Rice University. <a href="https://hdl.handle.net/1911/105531">https://hdl.handle.net/1911/105531</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/105531en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectprotein-DNA interactionen_US
dc.subjectfacilitated diffusionen_US
dc.subjectprotein search for targetsen_US
dc.subjectbackward master equationen_US
dc.subjectdiscrete-state stochastic frameworken_US
dc.titleTheoretical investigation of protein search for targets on DNAen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentChemistryen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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